Diffuse Optical Tomography (DOT) is a technique wherein tissue is illuminated at multiple source points on a tissue surface with light having wavelengths ranging from visible light to near infrared (NIR). Light transmitted through the tissue from each source point is detected at multiple reception points on the tissue surface, and a measure of attenuation (absorption and scattering) along paths from each source point to each reception point is obtained to estimate the chromophore, fluorophore or scatterer concentrations.
Modeling of the absorption and scattering creates potentially high contrast images containing functional tissue information. For example, the heme group of myoglobin and/or hemoglobin absorbs visible and near infrared light, and the spectral characteristics of the absorption vary noticeably with the degree of oxygenation. Therefore, high contrast may be obtained between portions of tissue containing high concentrations of heme (such as blood and muscle) and portions of tissue containing low concentrations of heme (such as fat), and between highly oxygenated and poorly oxygenated or infarcted tissues. In particular, the high vascularity of tumors often provides them a significant hemoglobin content and a potentially high intrinsic optical contrast between the tumor and normal tissue.
Scattering and absorption can, however, be difficult to distinguish when DOT is performed with monochromatic, continuous-wave radiation because the transmitted or reflected light is diffuse and intensity is generally low. Distinctions between background noise, scattering, and absorption, may be improved by the use of modulated illumination and AC-coupled amplification at multiple wavelengths. To produce the modulated light, most existing DOT systems use either amplitude modulated laser diodes or light-emitting diodes (LEDs) that operate at different wavelengths. However, there are a limited number of available wavelengths of laser diodes or LEDs that generate enough power to provide a high signal-to noise ratio and lase at wavelengths suitable for probing biological chromophores.
Tunable titanium-sapphire lasers have been used for studies of optical absorption in mammalian tissues. For example, “Optical biopsy of bone tissue: a step toward the diagnosis of bone pathologies”, Pifferi et al., Journal of Biomedical Optics 9(3), 474-480 (May/June 2004) describes using a mode-locked, tunable from 700 to 1000 nanometers wavelength, titanium-saphire (Ti:Saphire) pulsed laser and a dye laser tunable from 650 to 695 nanometers with a single 1 mm optical fiber for delivering light to a single point on a heel and a single 5 mm optical fiber bundle for receiving light from the heel and delivering the light to a time-resolved photomultiplier-tube photodetector.
Time resolved transmittance spectroscopy has also been used in optical spectrometry of soft tissues. “Absorption of collagen: effects on the estimate of breast composition and related diagnostic implications”, Taroni et al., Journal of Biomedical Optics 12(1), 014021 1-4 January/February 2007, describes absorption spectrometry of the breast. The apparatus of Taroni is probably similar to that used by co-author Pifferi. The apparatus of Taroni provides spectra of, for example, absorption along a single path between two points through the tissue. The apparatus of Taorni does not provide images resolving inclusions within the tissue. Taroni acknowledges that spectroscopy may have a role in imaging but does not discuss how this might be done and does not discuss alternative light detection approaches.